HX641 00910 
QP99.3.B5  Sco8  1914  The  content  of  sugar 


1 


Reprinted  from  the  American  Journal  of  Physiology 
Vol.  XXXIV— June  i,  1914— No.  Ill 


THE  CONTENT  OF  SUGAR  IN  THE   BLOOD   UNDER 
COMMON  LABORATORY  CONDITIONS 


By  ERNEST  LYMAN  SCOTT 


[From  the  Department  of  Phyeiclcgy  of  Columbia  Unb'ersity,  New  York] 


Submitted  in  partial  fulfilment  of  the  re'^nirements  for  the  degree  of  Doctor  of 
Philosophy,  in  the  Faculty  of  Pura  Science,  Columbia  University 


Reprinted  from  the  American   Journal  of  Physiology 

Vol.  XXXIV  — June    i,  1914  — No.  Ill 


THE   CONTENT  OF   SUGAR  IN   THE   BLOOD    UNDER 
COMMON  LABORATORY  CONDITIONS 


By  ERNEST   LYMAN   SCOTT 


[From  the  Department  of  Physiology  of   Columbia  University,  New  York] 


Submitted  in  partial  fulfilment  of  the  requirements  for  the  degree  of  Doctor  of 
Philosophy,  in  the  Faculty  of  Pure  Science,  Columbia  University 


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Sco2 


http://www.archive.org/details/contentofsugarinOOscot 


Reprinted  from  the  American  Journal  of  Physiology 
Vol.  XXXrV— June  i,  1914  — No.  Ill 


THE    CONTENT    OF    SUGAR    IN    THE    BLOOD    UNDER 
COMMON  LABORATORY   CONDITIONS 

By   ERNEST   LYMAN   SCOTT 

[From  the  Department  of  Physiology  of  Columbia  University,  New  York] 
Received  for  publication  April  18,  191 4 

I.  —  Introduction 

THE  use  of  variations  in  the  concentration  of  sugar  in  the  blood 
as  an  indication  of  the  response  of  the  animal  to  experi- 
mental conditions  offers  many  theoretical  advantages  over  the  use 
of  the  presence  of,  or  variations  in  the  amount  of,  sugar  in  the 
urine.  This  is  true,  first,  because  changes  in  either  direction  may 
be  detected.  While  sugar  is  always  present  in  the  blood,  it  is 
ordinarily  present  in  the  urine  in  minimal  quantities  only.  The 
urine,  therefore,  can  ordinarily  be  used  to  show  only  an  increase 
in  mobilized  sugar,  while  the  blood  will  show  either  an  increase  or 
a  decrease.  Secondly,  profound  changes  of  concentration  of  sugar 
may  occur  in  the  blood  without  giving  rise  to  a  detectable  glyco- 
suria. This  may  be  due  to  the  short  duration  of  the  change,  or  the 
change  may  not  be  of  suffi.cient  magnitude  to  lead  to  the  excretion 
of  sugar  by  the  kidneys  or  it  may  possibly  be  due  to  a  modification 
of  the  kidneys  themselves.  This  very  sensitiveness  may,  however, 
lead  to  serious  difficulties  in  the  handling  of  the  animals  before  and 
during  any  experiment  which  involves  the  estimation  of  sugar  in  the 
blood.  The  third  and  most  fundamental  advantage  lies  in  the  inti- 
mate relation  which  exists,  on  the  one  hand,  between  the  blood  and 
the  cells  which  are  using  the  sugar  and,  on  the  other,  between  the 
blood  and  the  stores  of  carbohydrate. 

Presumably  it  is  the  greater  difficulty  of  technique  which  has 
deterred  many  investigators  from  using  glycaemia  rather  than 
glycosuria,  as  the  criterion  of  change  in  the  organism.  Too  often 
this  has  detracted  greatly  from  the  value  of  the  research.  Others 
have  recognized  the  more  fundamental  bearing  of  variations  in  the 


272  Ernest  Lyman  Scott 

sugar  of  the  blood  but  apparently  without  recognizing  the  great 
delicacy  of  the  mechanism  with  which  they  were  working.  The 
result  is  that  in  many  cases  well-conceived  experiments  are  largely 
vitiated  by  inadequate  or  improper  controls.  Hirsch  and  Reinbach 
and  Roily  and  Opperman  ^  have  recently  called  attention  to  the 
necessity  of  controlling,  as  far  as  possible,  every  factor  in  experi- 
ments of  this  nature. 

The  purpose  of  this  paper  is  threefold:  first,  to  determine,  if 
possible,  a  set  of  conditions  under  which  the  amount  of  sugar  in 
the  blood  of  one  laboratory  animal,  the  cat,  will  be  approximately 
constant.  Upon  such  conditions,  when  once  established,  experi- 
mental conditions  may  be  superimposed  with  reasonable  assurance 
that  differences  from  the  constant  are  due  to  the  new  factors; 
secondly,  to  study  the  effects  of  some  of  the  common  conditions  to 
which  animals  are  subjected  before  being  submitted  to  the  experi- 
mental procedures  in  order  that  those  which  modify  the  concen- 
tration of  sugar  in  the  blood  may  be  determined;  and,  lastly,  to 
study,  for  the  same  reason,  a  few  of  the  experimental  procedures 
frequently  used  in  experiments  involving  the  estimation  of  the  sugar 
in  the  blood.  Abundant  evidence  from  the  literature,  as  well  as 
my  own  work,  shows  that  the  most  painstaking  attention  to  all 
details  is  demanded  if  trustworthy  results  are  to  be  obtained. 

Although,  as  will  be  seen  from  the  above,  the  experiments  to 
be  reported  were  not  primarily  planned  to  throw  light  upon  the 
problems  of  the  mobilization  and  use  of  sugar  by  the  organism,  it 
is  thought  that  some  of  the  results  found  may  have  a  deep  physi- 
ological significance.  An  extended  discussion  of  the  theoretical  or 
possible  significance  of  my  results  would,  however,  be  out  of  place 
at  this  time.  The  attempt  is  made  to  discover  and  catalogue  a 
few  of  those  disturbing  factors  which  are  constantly  entering  into 
our  experiments,  unbidden  and  frequently  without  our  knowledge, 
and  which  lead  us  to  false  conclusions.  Many,  perhaps  most,  of 
the  factors  studied  by  me  have  been  previously  investigated  for 
other  animals  and  indeed  some  of  them  for  the  cat.     It  was  never- 

1  References  to  the  literature  cited  will  be  found  in  Section  VII,  arranged 
alphabetically  according  to  authors.  Where  more  than  one  article  is  cited  from 
one  author  the  particular  articles  to  which  reference  is  made  is  indicated  by  the 
small  numbers. 


Content  of  Sugar  in  the  Blood  Under  Laboratory  Conditions     273 

theless  thought  desirable  to  correlate  the  results  for  a  single  animal 
and  by  a  single  uniform  method.  In  part  because  there  has  been 
comparatively  little  work  done  upon  the  cat,  and  in  part  for  the 
reasons  given  below,  this  animal  was  selected  for  the  research. 

Long  ago  Boehm  and  Hoffman  called  attention  to  some  of  the 
advantages  of  cats  for  laboratory  work.  They  mentioned  especially 
their  cleanly  habits,  their  uniform  size  and  the  fact  that  they  had 
found  them  to  be  more  uniformly  healthy  than  other  common 
animals  available  for  estimation  of  the  sugar  of  the  blood.  There 
are,  however,  other  and  perhaps  more  fundamental  advantages. 
A  large  amount  of  work  has  been  done  on  excised  muscles  —  a 
type  of  experiment  for  which  the  cat  seems  to  be  particularly 
adapted.  Notes  published  by  Lee  and  by  Lee  and  Harrold  show 
that  some  of  this  is  directly  related  to  the  use  of  sugar  by  the 
organism.  Again,  some  authors,  as  Macleod  and  Pearce,  have 
sought  to  avoid,  by  decerebration,  the  extended  use  of  drugs  in 
experiments  where  prolonged  anesthesia  is  necessary.  The  same 
results  may  be  obtained  in  a  more  physiological  manner,  and  with 
less  hemorrhage,  by  cerebral  anaemia.  Leonard  Hill  and  Stewart 
with  his  co-workers  have  shown  that  the  dog,  because  of  peculiar- 
ities of  the  blood-supply  to  the  brain,  is  not  so  well  adapted  for 
this  procedure  as  is  the  cat.  Pike  has  confirmed  Porter's  state- 
ments that  cats  are  better  adapted  for  experiments  involving  vaso- 
motor responses  than  are  dogs. 

II.  — ■  Method  of  Analysis 

The  preparation  of  the  animal  and  method  of  obtaining  the 
blood  will  be  discussed  later.  Only  the  chemical  processes  in- 
volved will  be  described  here.  It  is  not  possible  to  estimate  the 
sugar  by  any  known  method  in  the  presence  of  protein.  Many 
reagents  have  been  used  and  many  methods  proposed  for  the  re- 
moval of  the  protein  from  blood  preparatory  to  the  determination 
of  sugar.  In  1908  ]\IichaeHs  and  Rona  ^  proposed  the  use  of 
colloidal  iron  hydroxide  for  this  purpose.  Their  method  has  been 
well  received  and  is  widely  used  at  present.  Recently,  however, 
Lesser  reports  that  it  is  not  satisfactory,  in  the  form  proposed 
by   the   authors  for  the  blood  of  either  frogs   or   turtles.     In   the 


2  74  Ernest  Lyman  Scott 

limited  use  that  I  have  made  of  the  method  I  have  found  it  fairly- 
satisfactory  but  have  preferred  the  phosphotungstic  acid  method 
described  below.  A  method  which  requires  but  a  small  amount  of 
blood  for  the  analysis  possesses  many  obvious  advantages.  Be- 
cause of  this  the  method  recently  described  by  Lewis  and  Benedict 
or  the  micro-chemical  methods  of  Bang  or  of  Michaehs  will  prove 
of  great  value  to  both  the  chnician  and  the  experimentalist,  pro- 
vided that  they  give  the  same  satisfactory  results  in  other  hands 
that  have  been  reported  for  them  by  their  authors.  Dehn  and 
Hartman  are  now  pubhshing  a  series  of  researches  in  which  they 
are  developing  a  method  for  the  use  of  picric  acid  as  the  oxidizing 
agent  in  sugar  determinations.  Because  of  the  greater  deUcacy 
claimed  for  it  the  picric  acid  method  may  supplant  the  use  of  cop- 
per for  this  purpose.  The  method  which  I  have  used  is  very 
similar  to  the  one  used  by  Pfeffer  for  the  removal  of  proteins  from 
bacterial  cultures  prior  to  the  determination  of  sugar.  Reid  and, 
more  recently,  Oppler  have  described  methods  for  removing  the 
protein  from  blood  by  this  reagent. 

In  my  own  method  the  blood  was  drawn  directly  from  the 
blood-vessels  into  a  beaker  weighed  with  sufficient  i  per  cent  am- 
monium oxalate  to  make  the  final  concentration  of  oxalate  in  the 
blood  about  0.25  per  cent.  The  beaker  was  constantly  shaken  while 
the  blood  was  being  drawn.  The  second  weighing  was  made  at  once. 
Any  blood  on  the  sides  of  the  beaker  was  then  washed  down  with 
distilled  water  and  about  300  cc.  of  water  added.  This  was  done 
for  the  double  purpose  of  preventing  glycolysis,  as  suggested  by 
Rona  and  Dobhn,  and  of  breaking  down  the  corpuscles  so  that  any 
sugar  contained  within  them  might  be  freed.  This  was  suggested 
by  the  work  of  A.  Loeb,  Rona  and  Michaelis,-  Rona  and  Takahashi 
and  others.  As  soon  as  the  laking  appeared  complete  the  solution 
was  washed  into  a  500  cc.  volumetric  flask,  which  was  then  filled  to 
the  mark  with  distilled  water.  It  was  then  divided  into  two  equal 
portions  with  the  aid  of  a  250  cc.  flask,  and  each  portion  was  washed 
into  a  precipitation  jar.  About  1.2  cc.  of  a  freshly  prepared  10 
per  cent  solution  of  phosphotungstic  acid  was  then  added  for  each 
gram  of  blood  taken.  This  addition  was  made  slowly  from  a 
dropping  funnel  while  the  mixture  was  being  stirred  with  a  mechan- 
ical stirrer.     About  twenty  minutes  was  allowed  for  this  precipita- 


Content  of  Sugar  in  the  Blood  Under  Laboratory  Conditions     275 

tion,  but,  thanks  to  the  dropping  funnels  and  the  stirrers,  did  not 
consume  much  time  on  the  part  of  the  operator.  The  result  was 
a  brown  or  chocolate  colored  precipitate,  from  which  a  limpid 
filtrate  rapidly  separated,  that  gave  none  of  the  common  protein 
reactions.  After  the  precipitation  was  complete,  each  portion  was 
washed  into  a  500  cc.  flask,  which  was  then  filled  to  the  mark,  and 
filtered  through  an  ordinary  filter  without  suction.  An  aliquot  part 
of  about  350  cc.  was  taken  for  analysis. 

The  phosphotungstic  acid  was  removed  by  the  addition  of  25 
cc.  of  a  saturated  solution  of  barium  hydroxide.  After  this  addition, 
the  mixture  was  allowed  to  stand  for  a  time  at  room  temperature. 
It  must  not  be  heated  at  this  point,  nor  should  it  be  allowed  to 
stand  much  longer  than  is  necessary  to  complete  the  reaction. 
The  completion  of  the  reaction  was  determined  by  the  addition  of 
a  few  drops  of  the  barium  solution  to  a  few  cubic  centimeters  of 
the  clear  supernatant  fluid.  When  the  reaction  was  complete  it 
was  again  filtered  and  the  precipitate  was  well  washed  with  water. 
This  filtrate  was  rendered  just  acid  to  htmus  with  sulphuric  acid 
to  precipitate  the  excess  of  barium,  and  the  barium  sulphate  was 
removed  by  filtration.  The  final  filtrate  was  evaporated  to  about 
50  cc.  in  a  Jena  evaporating  dish,  and  the  sugar  was  estimated  by 
the  "Uniform  method  for  sugar  analysis"  described  by  Munsen 
and  Walker.  Calculations  were  made  from  the  tables  given  in 
Bulletin  107,  Edition  of  191 2,  of  the  Bureau  of  Chemistry,  United 
States  Department  of  Agriculture.  The  Bulletin,  in  addition  to 
the  table,  contains  a  brief  description  of  the  method. 

The  accurate  control  of  the  estimation  of  sugar  in  blood  or 
other  solutions  containing  protein  is  very  difficult.  The  present 
method  was  controlled  as  follows.  A  sample  of  blood  was  prepared 
as  described  above,  except  that  a  known  quantity  of  glucose  was 
added  to  one  of  the  two  portions  just  before  the  precipitation  was 
begun.  From  this  time  on  the  estimation  was  completed  in  the 
usual  manner.  Evidently  the  amount  of  sugar  recovered  from  the 
portion  to  which  the  addition  was  made,  less  the  amount  added, 
should  be  equal  to  that  recovered  from  the  other  portion.  Refer- 
ence to  Table  i  will  show  that  this  was  the  case  within  the  Hmits 
of  error  permissible  for  work  of  this  type.  This  method  presupposes 
that  the  added  sugar  exists  in  the  blood  in  the  same  condition  as 


276 


Ernest  Lyman  Scott 


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Content  of  Sugar  in  the  Blood  Under  Laboratory  Conditions     277 

that  naturally  present  —  a  presumption  which  is  by  no  means 
proved.  For  this  reason,  even  though  the  results  are  satisfactory, 
one  cannot  be  sure  that  all  of  the  sugar  has  been  recovered. 

The  degree  to  which  results  obtained  by  any  one  method  are 
consistent,  one  with  another,  gives  another  means  of  judging  of  the 
accuracy  of  the  method.  The  reader  will  have  to  be  the  judge  of 
the  way  in  which  the  present  method  responds  to  this  test  after 
having  studied  the  tables  submitted  —  especially  Table  5. 

Rona  and  IMichaelis  ^  have  compared  different  methods  for  the 
removal  of  protein  from  blood  and  have  found  a  variation  in  the 
amount  of  sugar  recovered  after  the  use  of  the  several  methods. 
This,  they  beheve,  is  because  the  glucose  does  not  all  exist  in  the 
blood  in  simple  solution.  There  is  no  present  need  for  postulating 
the  exact  condition  of  the  sugar,  since  any  aggregation  of  the  car- 
bohydrate molecules  or  any  combination  of  them  with  either  pro- 
tein or  lipoid  might  easily  interfere  with  the  complete  recovery  of 
the  dextrose  by  any  of  the  methods  available. 

Somq  authors,  notably  Arthus,  and  Rosenfeld  and  Asher,  have 
sought  to  show,  by  dialysis,  that  the  sugar  exists  in  the  blood  in 
simple  solution.  Consideration  of  the  law  of  mass  action,  however, 
reveals  the  limitations  of  this  method  of  attack.  The  equilibrium 
is  at  once  destroyed  by  the  removal  of  any  portion  of  the  sugar 
which  may  be  in  true  solution.  The  disturbed  condition  will  bring 
about  a  continuous  dissolution  of  any  loose  combinations  present 
so  long  as  the  removal  occurs.  In  this  way  it  is  conceivable  that  a 
great  deal  of  sugar  may  be  removed  by  dialysis  which  did  not 
originally  exist  in  free  solution. 

From  these  considerations  it  follows  that  before  the  work  of 
different  authors  or  the  results  obtained  by  different  methods  may 
be  compared,  a  factor  of  comparison  must  be  estabhshed.  That  is, 
the  amount  of  sugar  recoverable  from  the  same  blood  by  each  of 
the  methods,  under  the  same  conditions,  must  be  found,  and  the 
resulting  ratios  considered  in  making  comparisons. 

If  it  is  true  that  the  form  in  which  the  sugar  is  present  in  the 
blood  influences  the  amount  recoverable  by  the  different  methods, 
it  follows  that  the  amount  recoverable  by  one  and  the  same  method 
may  be  expected  to  vary  with  the  variation  of  the  condition  of  the 
sugar  or  of   any  of  its  combinations  which  occurs  as  a  result  of 


278  Ernest  Lyman  Scott 

experimental  procedures.  Thus,  the  difficulty  of  interpretation  of 
results  all  of  which  are  obtained  by  the  same  method  is  also  in- 
creased. We  have  at  present  no  means  of  knowing  that  the  sugar 
exists  in  the  blood  in  the  same  state  under  different  experimental 
conditions  to  which  the  animal  has  been  exposed.  Thus  a  rise  or 
fall  in  recoverable  sugar  following  any  experimental  change  to  which 
the  animal  may  have  been  subjected,  may  be  due  to  a  change  in 
the  condition  of  the  sugar  in  the  blood  with  no  variation  in  the 
absolute  amount. 

These  possibilities  of  misinterpretation  must  be  kept  in  mind  in 
studying  the  following  results. 

III.  —  The  Effect  of  Some  of  the  Preliminary  Conditions 
UPON  THE  Concentration  of  Sugar  in  the  Blood 

Under  this  head  will  come  only  those  factors  which,  apart  from 
the  actual  experimental  conditions,  interfere  with  the  concentration 
of  sugar.  , 

The  changes  in  environment  undergone  by  an  animal  on  enter- 
ing the  laboratory  cannot  be  presumed  to  be  without  influence 
upon  the  point  in  question.  Hence,  if  uniform  results  are  to  be 
expected,  sufficient  time  must  be  allowed  for  all  of  the  animals  to 
establish  themselves  in  equilibrium  with  their  new  surroundings. 
Of  the  many  factors  that  might  play  a  part  in  bringing  about  varia- 
tions, two  seemed  especially  liable  to  do  this.  These  were,  first, 
the  changes  in  the  character  of  the  diet  and  feeding  habits,  and, 
secondly,  the  mental  excitement  incident  to  the  new  conditions. 
Time  must  be  allowed  the  animals  to  establish  themselves  upon 
their  new  diet  and  to  become  accustomed  to  their  new  environ- 
ment. Of  the  two,  very  probably  the  latter  is  the  more  productive 
of  variations.  A  week  seemed  none  too  long  a  time  to  allow  to  the 
animals  for  this  purpose,  and  hence  was  taken  as  the  minimum 
limit  in  the  usual  routine.  The  few  animals  which  were  killed 
after  a  shorter  period  in  the  laboratory  will  be  specially  mentioned 
in  the  tables. 

In  Table  2  it  is  shown  that  the  physical  condition  may  be  a 
disturbing  factor.  Here  it  is  seen  that  the  concentration  of  sugar 
may  be  high,  as  in  numbers  58,   74  and   106,  or  be  in  essential 


Content  of  Sugar  in  the  Blood  Under  Laboratory  Conditions     279 


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28o  Ernest  Lyman  Scott 

harmony  with  that  of  normal  animals  as  shown  by  numbers  60 
and  61;  again  in  one  case,  number  95,  which  had  apparently  been 
running  for  a  long  time,  the  concentration  was  low.  From  this  it 
is  evident  that  one  of  the  conditions  for  concordant  results  is  the 
rigid  exclusion  of  all  animals  which  are  not,  so  far  as  can  be  de- 
termined, in  good  health.  While,  as  was  shown  above,  a  certain 
minimal  stay  in  the  laboratory  should  be  allowed  all  animals  before 
the  sample  is  taken,  too  long  a  preparatory  period  is  not  desirable. 
The  animals  in  general  do  not  do  as  well  in  confinement  as  when 
free,  and  become  especially  liable  to  infection.  For  this  reason, 
too,  in  experiments  of  long  duration  great  care  must  be  taken  to 
protect  the  animal  from  all  forms  of  infection  and  other  influences 
which,  aside  from  the  purely  experimental  conditions,  might  lead 
to  a  changed  physical  condition. 

The  length  of  the  period  intervening  between  the  last  feeding 
and  the  collection  of  the  blood  may  be  an  important  factor. 
Bang  and  others  have  fed  animals  varying  amounts  of  different 
carbohydrates  in  solution,  and  have  followed  the  resulting  changes 
in  the  concentration  of  sugar  in  the  blood.  Boe  agrees  with  Bang 
that  the  hyperglycaemia  induced  in  rabbits  by  this  means  has 
disappeared  by  the  end  of  the  third  hour.  Fischer  and  Wishart 
report  a  return  to  normal,  in  dogs  which  have  ingested  fifty  grams 
of  glucose  in  solution,  by  the  end  of  the  second  hour.  There  is  no 
doubt  but  that  such  experiments  are  of  great  value  in  determining 
the  changes  in  glycaemia  which  take  place  under  the  conditions  of 
the  experiment.  However,  conclusions  as  to  the  conditions  follow- 
ing an  ordinary  meal  must  be  drawn  with  caution,  since  the  time 
relations  following  the  ingestion  of  protein  and  fat,  or  of  these  with 
starch,  are  not  necessarily  the  same.  This  is  true  not  only  because 
of  the  different  quantities  of  carbohydrate  taken  into  the  body 
under  the  different  conditions,  but  also  because  of  the  difference 
in  rates  of  absorption  dependent  upon  the  necessity  for  digestion 
in  the  usual  meal  and  the  interference  arising  from  the  other 
elements  of  the  meal.  In  any  case,  it  was  thought  best  to  allow 
sufficient  time  for  any  passing  disturbance  to  disappear.  With 
two  exceptions  the  animals  were  allowed  to  live  from  sixteen  to 
twenty-four  hours  after  the  last  meal  before  the  sample  of  blood 
was   taken.     In   a   number   of   cases   the   alimentary   canals   were 


Content  of  Sugar  in  the  Blood  Under  Laboratory  Conditions     281 

examined  and  found  empty  as  far  as  the  ileocoecal  valve.  Each 
of  the  two  exceptions  noted  above  were  killed  three  hours  after  a 
meal,  one  of  meat,  the  other  of  bread  and  meat.  The  one  which 
had  received  meat  alone,  number  77,  yielded  0.066  per  cent  sugar, 
which  is,  as  will  be  seen  by  comparing  with  Table  5,  in  approximate 
agreement  with  the  standard.  The  other  cat,  number  76,  yielded 
a  concentration  of  0.086  per  cent.  This  should,  of  course,  be  com- 
pared with  the  results  shown  in  Table  4.  When  this  is  done  it  is 
seen  that  it  is  well  within  the  limits  of  variation.  Hence  no  signifi- 
cance can  be  attached  to  the  variation  in  a  single  experiment  from 
the  average  —  0.078  per  cent  —  which  is  found  for  the  correspond- 
ing series. 

There  seems  to  be  some  difference  of  opinion  with  regard  to  the 
effect  of  the  character  of  the  diet.  Seehg  finds  less  disturbance  of 
the  concentration  of  sugar  in  the  blood  of  dogs  given  ether  when 
the  diet  has  consisted  of  bread  for  several  days  than  when  it  has 
consisted  largely  of  meat.  As  this  point  is  of  so  much  importance 
to  the  experimentahst,  some  attention  was  given  to  it.  A  diet 
consisting  only  of  bread  was  found  to  be  impractical  for  cats,  so 
that  they  were  given  stale  bread  and  cooked  beef  hearts,  approxi- 
mately pound  for  pound,  together  with  the  water  in  which  the 
hearts  were  cooked.  Even  on  this  diet  the  animals  did  not  do  so 
well  and  were  more  subject  to  respiratory  infection  than  those 
receiving  the  diet  to  be  described  later.  It  was  not  usually  possi- 
ble to  keep  them  in  a  satisfactory  condition  on  this  diet  for  a 
longer  time  than  two  weeks.  Aside  from  this,  or  perhaps  because 
of  it,  a  constancy  of  results  for  the  quantity  of  sugar  in  the  blood 
could  not  be  obtained  which  approached  that  with  the  other  diet. 
The  results  obtained  are  summarized  in  Table  4.  It  will  be  noticed 
that  the  variation  between  the  extremes  —  0.056  per  cent  and 
0.104  per  cent  —  is  equal  to  86  per  cent  of  the  smaller  number  and 
that  83  per  cent  vary  from  the  average  of  the  series  by  more  than 
10  per  cent.  Evidently  this  is  not  a  satisfactory  diet  where  a 
constant  concentration  of  sugar  is  the  end  sought. 

The  other  diet  was  cooked  beef  hearts  with  the  bread  omitted. 
This  was  found  to  be  more  satisfactory.  While,  as  seen  from  Table 
5,  the  extreme  variation  is  between  0.096  per  cent  and  0.056  per 
cent  and  is  thus  almost  as  great  as  the  variation  of  the  previous 


282  Ernest  Lyman  Scott 

series,  only  25  per  cent  of  the  animals  vary  from  the  mean  by  more 
than  10  per  cent.     Cf.  Table  9. 

Why  the  average  for  the  animals  allowed  carbohydrate  food  in 
addition  to  the  meat  should  be  higher  than  that  for  those  given 
meat  alone,  is  a  question  difficult  of  answer.  According  to  the 
ideas  generally  held,  the  character  of  the  food  is  immaterial  beyond 
the  first  few  hours  after  the  meal.  Further,  if  the  difference  is  due 
directly  to  the  differences  of  diet,  one  would  not  look  for  the  ex- 
treme variations  which  were  found.  There  are  other  possibihties, 
however.  Reference  to  Table  2  shows  that  animals  with  some  types 
of  infection  seem  to  have  a  relatively  higher  content  of  sugar  than 
the  standard  animals.  As  above  noted,  animals  fed  on  the  bread 
and  meat  diet  are  more  prone  to  infection,  and  it  is  possible  that 
in  some  cases  incipient  disease  was  overlooked.  Again  these  ani- 
mals were  more  restless  and  quarrelsome  than  those  on  the  meat 
diet,  and  this  would  tend  toward  higher  results.  Rose  thinks  that 
carbohydrate  feeding  does  not  materially  increase  the  amount  of 
sugar  in  the  blood  of  rabbits.  It  is,  though,  well  to  note  in  this 
connection  that  the  rabbit  is  a  herbivore,  and  as  such  may  have 
better  provision  for  handling  carbohydrates  than  the  cat,  which  is 
by  nature  a  strict  carnivore.  One  experiment  reported  by  Roily 
and  Opperman  ^  indicates  that  it  is  immaterial  whether  the  protein 
given  to  the  dog  is  derived  from  animal  or  vegetable  sources. 
Jacobsen's  ^  results  are  also  of  interest  here. 

It  has  long  been  known  that  the  more  intense  emotions  are  a 
frequent  cause  of  glycosuria.  This  was  early  spoken  of  by  Rayer 
and  somewhat  later  by  Frerichs.  Recently  Cannon  and  some  of 
his  co-workers  have  laid  especial  stress  upon  this  form  of  glyco- 
suria; and  have  shown  that  for  cats  at  least  it  is  of  purely  psycho- 
logical origin.  Pavy  ^  speaks  of  the  necessity  for  "tranquillity" 
on  the  part  of  the  animal  while  the  sample  is  being  drawn,  and 
Eckhard  emphasizes  the  fact  that  rabbits  must  not  be  tied  in  the 
holder  for  work  involving  glycosuria.  Naunym  very  early  reported 
an  increased  amount  of  sugar  in  the  blood  of  animals  which  had 
been  bound.  Among  the  later  writers  Jacobsen,^  Hirsch  and 
Reinbach  and  Loewy  and  Rosenberg  ^  have  discussed  in  detail 
many  of  the  difficulties  in  the  way  of  the  use  of  rabbits  for  experi- 
ments, of  this  type.    Presumably  this  difiiculty  hes,  in  large  part  at 


Content  of  Sugar  in  the  Blood  Under  Laboratory  Conditions     283 

least,  in  the  nervous  disposition  of  these  animals  and  their  prone- 
ness  to  excitement.  Roily  and  Opperman^'^  discard  them  as 
entirely  unsuited  for  such  work.  Seelig  finds  no  glycosuria  in  one 
dog  which  had  been  bound  for  two  and  one-half  hours.  Roily  and 
Opperman  ^  also  think  that  dogs  may  be  safely  used  for  such  ex- 
periments, while  Loewy  and  Rosenberg  on  the  other  hand  find  the 
concentration  of  sugar  in  the  blood  of  both  dogs  and  of  rabbits 
increased  by  sensory  stimulation,  though,  it  is  true,  the  increase  in 
the  dogs  was  not  so  marked. 

Boehm  and  Hoffmann  first  demonstrated  glycosuria  in  cats  as  a 
result  of  binding  them  on  a  holder  and  so  called  it  "Fesselung 
Diabetes."  This  result  has  been  interpreted  as  being  due  to 
various  factors,  as  mental  excitement,  loss  of  heat,  and  muscular 
exertion.  It  has  been  shown  in  Cannon's  laboratory  that  the  first 
factor  alone  is  sufficient.  He  therefore  suggests  the  term  "emo- 
tional glycosuria."  The  general  fact  that  hyperglycaemia  and 
frequently  glycosuria  follow  excitement  in  all  laboratory  animals, 
with  the  possible  exception  of  the  dog,  and  in  man  is  widely  ac- 
cepted. The  only  reason  for  adding  to  the  already  extended 
literature  of  the  subject  is  to  find  to  what  extent  the  handling  of 
an  animal  which  is  necessary  for  obtaining  a  sample  of  blood  or  in 
preparing  it  for  an  experiment  may  disturb  the  standard  conditions. 
In  my  experiments,  all  animals  in  which  excitement  was  evident 
were  discarded,  except  as  noted  in  the  tables.  A  few  in  which 
excitement  was  evident  were  killed,  and  the  results  proved  the 
necessity  of  Pavy's  rule  of  complete  tranquilhty  if  consistent  find- 
ings are  desired.  Two  animals,  numbers  108  and  no,  were  held, 
as  if  given  ether  by  a  cone,  though  ether  was  not  actually  given  in 
either  case.  A  third  was  placed  in  a  bell  jar  for  about  the  length 
of  time  that  would  ha,ve  been  required  for  etherization,  had  ether 
been  given.  Others  were  subjected  to  other  conditions  which  are 
apt  to  occur  in  the  laboratory  and  which  produced  sHght  excite- 
ment, as  indicated  by  crying  or  otherwise.  The  results,  with  a 
brief  description  of  the  conditions  in  each  case,  are  given  in  Table 
3.  It  will  be  seen  that  in  every  case  there  is  a  noticeable  rise  in 
the  amount  of  sugar  contained  in  the  blood.  These  results  show 
that  the  animal  must  be,  as  Pavy  says,  tranquil,  not  alone  at  the 
time  that  the  sample  is  drawn,  but  for  some  time  before.     From 


284 


Ernest  Lyman  Scott 


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Content  of  Sugar  in  the  Blood  Under  Laboratory  Conditions     285 

what  has  been  said,  it  will  be  seen  that  those  experiments  in  the 
past  in  which  the  blood  has  been  drawn  from  an  artery  or  vein 
without  anesthetics  have  a  very  doubtful  value,  since  it  is  hardly 
probable  that  an  animal  will  undergo  such  an  operation  and  remain 
in  perfect  tranquillity.  The  necessary  restraint  is  of  itself  suffi- 
cient to  influence  the  results  as  indicated  by  animals  number  108 
and  no.  Of  the  disturbing  effect  of  anesthetics  more  will  be  said 
later.  There  remains  then  only  the  possibility  of  rapidly  killing 
the  animal  with  the  least  possible  excitement  and  the  rapid  with- 
drawal of  the  sample  of  blood  after  death.  This  was  long  ago 
appreciated  by  Pavy,  who  killed  his  animals  by  pithing  with  a 
Bernard  needle  and  then  collected  the  blood  from  the  heart  or 
from  the  thoracic  cavity  after  severing  the  large  blood  vessels. 
Sudden  decapitation  and  collection  of  the  blood  from  the  severed 
neck  vessels  seemed  to  offer  some  advantages  over  Pavy's  method, 
and  was  used  throughout  the  present  work.  The  interval  during 
which  the  animal  was  held'  before  decapitation  seldom  exceeded 
three  seconds,  while  about  fifteen  to  twenty  seconds  more  were 
required  for  the  collection  of  the  blood.  As  a  further  precaution 
against  excitement,  an  attendant,  from  whom  the  animals  were 
accustomed  to  receive  food,  brought  them  to  the  laboratory  and 
assisted  throughout  the  preparation  of  the  animal  and  the  collec- 
tion of  the  blood. 

That  the  amount  of  blood  drawn  relative  to  the  total  amount  in 
the  body  may  affect  the  concentration  of  sugar  in  the  sample  seems 
to  have  been  overlooked  by  previous  investigators.  In  studying 
this  relationship  a  number  of  standard  experiments  were  tabulated 
in  the  order  of  the  increasing  amounts  of  blood  drawn,  when  this 
was  expressed  in  grams  per  kilo  of  body  weight.  It  was  then 
found  that  the  respective  concentrations  of  sugar  were  arranged  in 
the  reverse  order:  that  is,  the  more  blood  drawn  per  kilo  of  body 
weight,  the  lower  is  its  concentration  of  sugar.  This  is  wholly 
independent  of  the  actual  amount  of  blood  drawn,  as  is  shown 
below.  The  phenomenon  is  somewhat  surprising  since  we  know 
that  hemorrhage  under  certain  conditions  causes  hyperglycaemia. 
The  relationship  of  which  we  are  speaking,  however,  is  not  to  be 
confused  with  the  so-called  "hemorrhage  hyperglycaemia"  as 
that  term  is  commonly  used. 


286  Ernest  Lyman  Scott 

In  the  curve  shown  in  figure  i  the  data  are  derived  from  Table 
5.  Unfortunately  the  body  weights  of  the  animals  used  in  the 
earher  experiments  were  not  recorded,  hence  these  experiments  are 
not  available  for  our  present  use.     The  amounts  of  blood  drawn 

0.100 


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0.060 


0.050 


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50 

Figure  1 


40 


per  kilo  of  body  weight  are  plotted  on  the  x-axis.  The  concentra- 
tions of  sugar  in  the  blood,  expressed  in  grams  per  cent,  were 
plotted  on  the  ^'-axis.  Provisionally  the  line  represented  by  the 
equation  x/a  +  y/h  =  i  is  taken  as  representing  the  relation  found. 
In  the  equation  x  and  y  are  variables;    x  represents  the  amounts 


Content  of  Sugar  in  the  Blood  Under  Laboratory  Conditions     287 

of  blood  drawn  per  kilo  of  body  weight,  and  y  the  concentrations 
of  sugar  in  the  blood,  a  and  h  are  constants  whose  values  have 
not  been  exactly  determined,  but  which  approximate  133  and 
0.084  respectively. 

If  this  relationship  between  the  amount  of  blood  drawn  and  its 
concentration  of  sugar  is  constant  from  one  animal  to  another,  and 
if  the  above  formula  is  its  true  expression,  ;y  is  a  constant  in  the 
equation  y  =  h  {%'  —  x)  /  a  -{-  y' ;  where  a  and  h  have  the  values  as- 
signed to  them  above,  x'  and  y'  represent  respectively  the  amount 
of  blood  drawn  per  kilo  of  body  weight  and  its  concentration  of 
sugar  in  any  particular  experiment,  x  may  have  any  arbitrary 
value.  Under  these  circumstances  y  represents  the  concentration 
which  would  have  been  found  had  x  grams  of  blood  per  kilo  of 
body  weight  been  drawn.  This  calculation  has  been  made  for  a 
number  of  the  experiments,  x  being  taken  as  equal  to  30.  The 
results,  when  recorded  in  the  tables,  are  found  in  the  column  headed 
values  calculated  for  30  grams  per  kilo  body  weight.  Since  there 
have  not  been  enough  estimations  made  to  v/arrant  the  assignment 
of  exact  values  to  a  and  h,  the  optimum  position  of  the  curve  was 
ascertained  by  trial  and  the  values  were  found  mechanically  after 
having  plotted  the  results  on  coordinate  paper  as  for  figure  i .  The 
results  for  the  standard  animals,  calculated  in  the  manner  just 
described,  are  given  in  Table  5,  column  10.  A  comparison  of 
columns  7  and  10  of  this  table  shows,  first,  that  the  mean  for  the 
series  has  not  been  modified;  secondly,  that  the  difference  between 
the  highest  and  the  lowest  results  for  the  eleven  animals  compared 
is  greatly  reduced.  Again  the  number  of  individuals  which  vary 
from  the  mean  by  more  than  10  per  cent  is  reduced  from  4  to  i,  or 
from  36  per  cent  to  9  per  cent  of  the  whole  number  of  animals 
compared.  Thus  it  v/ill  be  seen  that  in  general  the  calculated 
values  approach  still  closer  to  a  constant  than  do  those  derived 
directly  from  the  analysis. 

In  order  to  test  this  relationship  still  further  the  blood  was 
drawn  from  four  animals  in  a  series  of  samples  in  each  of  which  the 
sugar  was  determined.  The  results  obtained  confirm  those  ob- 
tained by  the  former  method  and  are  given  in  Table  6.  A  study  of 
this  table  reveals  that  in  every  case,  with  the  exception  of  the  third 
sample  in  experiment  95,  the  concentration  of  sugar  in  any  sample 


288  Ernest  Lyman  Scott 

in  the  series  is  lower  than  for  any  sample  in  the  same  series  pre- 
viously drawn.  These  results  do,  however,  indicate  that  the  curve 
representing  the  relation  is  not  a  straight  line,  but  that  it  falls 
more  rapidly  at  first  than  it  does  later. 

It  was  suggested  that  this  relationship  is  due  only  to  an  error 
in  analytical  technique  and  so  is  of  no  physiological  significance. 
For  instance,  it  might  be  that  a  greater  percentage  of  the  sugar  is 
recovered  when  only  small  amounts  of  blood  are  used.  While  it  is 
true  that  such  an  error  might  lead  to  somewhat  similar  results,  the 

TABLE   4 

The  Effect  of  a  Diet  of  Bread  and  Meat  upon  the  Concentration  of 
Sugar  in  the  Blood  of  Cats 


No. 

of 

Exp. 

Sex 

Days 
on 
diet 

Body 
wt.  k. 

Blood 

drawn 

gm. 

Blood 

per  k. 

body  wt. 

gm. 

Gm.  % 
glucose 
recov- 
ered 

Var.  from  stan- 
dard mean- 
table  5 

Values  cal.  for 

30  gm.  blood  per 

k.  body  wt. 

Absolute 

%of 
mean 

Concen- 
tration 
gm.% 

Var.  % 
of  stan- 
dard 

45 

F 

24 

2.50 

93.29 

37.12 

0.100 

+  0.031 

45 

0.105 

+  52 

46 

M 

12 

2.94 

101.42 

34.50 

0.070 

+  0.001 

1 

0.073 

+    6 

53 

M 

24 

2.98 

83.62 

28.06 

0.104 

+  0.035 

51 

0.102 

+  48 

54 

F 

24 

2.75 

79.55 

28.93 

0.060 

-  0.009 

13 

0.059 

-  14 

55 

M 

24 

2.50 

72.66 

29.06 

0.056 

-0.013 

19 

0.056 

-  19 

56 

M 

18 

2.94 

65.22 

22.18 

0.080 

+  0.011 

16 

0.075 

+    9 

Mean 

0.078 

+  0.009 

13 

0.078 

+  13 

criticism  cannot  be  valid  for  three  reasons.  First,  it  has  been 
found  that  when  the  sugar  in  unequal  samples  of  the  same  blood 
was  determined,  slightly  smaller  concentrations  were  found  in  the 
smaller  samples.  This  was  probably  due  to  some  slight  negative 
error  which  has  a  tendency  to  be  constant.  This  error  would  be 
multiphed  by  a  larger  factor  when  the  absolute  amounts  recovered 
were  computed  to  percentages  and  so  lead  to  the  smaller  concentra- 
tions found  in  the  smaller  samples  of  blood.  Thus  it  will  be  seen 
that  in  so  far  as  this  error  would  have  any  tendency,  it  would  be  to 


Content  of  Sugar  in  the  Blood  Under  Laboratory  Conditions     289 

hide  the  relationship  found  rather  than  to  simulate  it.  Secondly,  the 
effect  is  the  same  whether  the  variation  in  the  amount  of  blood  per 
kilo  of  body  weight  is  brought  about  by  drawing  different  amounts 
of  blood  from  animals  of  approximately  the  same  weight  or  by  draw- 
ing the  same  amounts  of  blood  from  animals  of  different  weights. 
Compare   experiments   59   with   91,    and   69   with   89   in  Table   5. 

TABLE   5 

The  Concentration  of  Sugar  in  Cat's  Blood  under  the  Conditions  which 
Were  Selected  as  Standard 


Blood 

Gm.% 

Var.  from  standard 
mean,  table  5 

Values  cal.  for  30 

gm.  blood  per 

k.  body  wt. 

No. 
of 

Sex 

Days 
on 

Body 

wt. 

Blood 
dra^vn 

per  k. 
body  wt. 

glucose 
re- 

Exp. 

diet 

k. 

gm. 

gm. 

covered 

%of 
mean 

Concen- 

Var. % 

Absolute 

tration 
gm.  % 

of  stan- 
dard 

12 

M 

1 

— 

97.86 

— 

0.062 

-  0.007 

10 

— 

— 

13 

M 

1 

— 

94.36 

— 

0.076 

+  0.007 

10 

— 

— 

15 

— 

1 

— 

129.73 

— 

0.063 

-  0.006 

9 

— 

— 

16 

— 

1 

— 

60.94 

— 

0.063 

-  0.006 

9 

— 

— 

23 

— 

5 

— 

116.33 

— 

0.070 

+  0.001 

1 

— 

— 

47 

F 

9 

2.00 

84.07 

42.04 

0.056 

-  0.013 

19 

0.064 

-    7 

48 

F 

14 

2.66 

86.10 

32.37 

0.061 

-  0.008 

12 

0.063 

-    9 

49 

F 

16 

2.46 

66.28 

26.94 

0.072 

+  0.003 

4 

0.070 

+    1 

50 

M 

16 

4.96 

125.31 

25.26 

0.074 

+  0.005 

7 

0.071 

+    3 

59 

I\I 

14 

3.16 

122.95 

38.91 

0.059 

-  0.010 

15 

0.064 

-    7 

68 

F 

18 

3.25 

55.80 

17.17 

0.096 

+  0.027 

39 

0.088 

+  28 

69 

F 

16 

2.19 

66.77 

30.49 

0.066 

-  0.003 

4 

0.066 

-    4 

89 

F 

6 

3.65 

65.84 

18.04 

0.075 

+  0.006 

9 

0.068 

-    1 

91 

M 

25 

3.05 

39.56 

12.97 

0.074 

+  0.005 

7 

0.062 

+  10 

103 

M 

8 

2.23 

62.61 

28.08 

0.070 

+  0.001 

1 

0.069 

±    0 

107 

F 

10 

2.25 

68.35 

30.38 

0.073 

+  0.004 

6 

0.073 

+    6 

Mean 

— 

— 

2.93 

83.93 

27.38 

0.069 

— 

— 

0.069 

— 

290  Ernest  Lyman  Scott 

Thirdly,  if  the  figures  given  in  Table  6  are  compared,  it  will  be 
seen  that  the  progressive  decrease  in  concentration  is  entirely  inde- 
pendent of  the  absolute  amount  of  blood  drawn. 

No  experiments  have  yet  been  made  to  determine  the  physio- 
logical significance  of  this  decrease  in  the  concentration  of  sugar 
when  a  larger  proportion  of  the  total  blood  is  drawn  at  one  time. 
The  most  plausible  explanation  which  occurs  to  me  is  that  it  is 
due  to  the  leaching  of  the  tissue  fluids  into  the  blood  vessels  which 
occurs  during  severe  hemorrhage.  Evidence  as  to  whether  such 
a  leaching  does  occur  could  be  obtained  by  making  simultaneous 
estimations  of  the  sugar  and  the  hemoglobin  in  the  blood.  Varia- 
tions of  the  viscosity  of  the  blood  might  also  be  used  to  throw  light 
upon  this  question.  Professor  Burton-Opitz  has  found  that  blood 
drawn  25  to  30  minutes  after  a  severe  hemorrhage  has  a  lower 
viscosity  than  that  drawn  before  the  hemorrhage.  More  than  this, 
he  assures  me  ^  that  from  his  experience  he  would  expect  that  the 
last  of  a  large  amount  of  blood  drawn  at  one  time  would  have  a 
noticeably  lower  viscosity  than  would  the  first  portions.  This 
harmonizes  directly  with  the  theory  advanced  above. 

Increased  concentrations  caused  by  the  usual  methods  of  with- 
drawal of  blood  have  without  doubt  been  the  reason  why  the  effect  of 
the  relative  amount  of  hemorrhage  upon  the  concentration  of  sugar 
in  the  blood  has  been  so  long  overlooked.  Factors  are  introduced  by 
these  methods  which  cause  a  greater  or  less  discharge  of  the  stores 
of  glycogen,  and  so  any  small  diminution  in  the  concentrations  of 
sugar  in  the  blood  is  hidden.  Pavy's  method  of  collection  should 
give  the  same  results  as  mine,  provided  all  the  blood  which  has 
flowed  from  the  vessels  up  to  the  time  of  collection  is  analyzed. 
However,  I  have  been  unable  to  find  all  of  the  necessary  data  in 
any  of  his  tables.  Schenck  reports  a  very  small  difference  between 
the  first  and  second  of  two  consecutive  samples.  In  two  experi- 
ments, the  concentration  of  sugar  in  the  second  sample  was  less 
than  in  the  first,  and  in  one  experiment,  greater.  Anderson,  in 
two  different  experiments,  finds  almost  the  same  concentration  of 
sugar  in  each  of  three  consecutive  samples  of  blood.  The  later 
samples  have,  however,  a  shghtly  greater  concentration  of  sugar 
than    the   earher   ones.     Pavy  ^    reports   an   increased    amount   of 

1  Personal  communication. 


Content  of  Sugar  in  the  Blood  Under  Laboratory  Conditions     291 

sugar  in  the  later  samples  of  bullock's  blood  whether  the  animals 
were  killed  by  the  Jewish  or  by  the  pole-axe  method.  In  none  of 
the  above  were  the  samples  so  obtained  that  the  discharge  of  stored 
glycogen  would  have  been  prevented. 

Though  probably  sex  of  itself  has  no  influence  upon  the  concen- 
tration of  sugar  in  the  blood  (cf.  Bang),  it  is  quite  possible  that 
the  greater  excitability  of  the  male  cats  which  Cannon  ^  has  found 
to  exist  may  operate  through  the  mechanism  for  emotional  glyco- 
suria to  simulate  such  an  influence.  If  this  were  true,  it  would  be 
especially  noticeable  in  experiments  which  involve  much  handling 
of  the  animal  or  its  confinement  in  apparatus.  While  for  animals 
kept  under  standard  conditions  I  have  found  the  mean  for  females 
slightly  higher  than  that  for  males,  the  difference  is  small.  More- 
over, the  nature  of  the  individual  variations.  Tables  4  and  5,  make 
one  hesitate  to  attach  any  significance  to  this  slight  difference.  It 
is  quite  possible  that  the  results  would  have  been  otherwise  for  a 
series  of  animals  confined  in  some  apparatus,  as  a  respiration 
chamber,  for  a  period  of  time.  The  only  evidence  that  I  have  on 
this  is  drawn  from  two  animals  which  were  confined  in  a  small 
cage  and  exposed  to  a  lowered  temperature  for  a  period  of  two 
hours.  A  small  female  cat,  number  92,  Table  3,  resented  the  treat- 
ment and  yielded  a  concentration  of  0.149  P^r  cent  of  sugar,  while  a 
large  male,  number  93,  was  apparently  tranquil  throughout  the 
period,  and  yielded  a  result  even  lower  than  usual,  0.049  P^r  cent. 
It  seems  to  me  that  the  stress  should  be  laid  upon  the  nature  of 
the  particular  individual,  rather  than  in  blindly  choosing  animals 
of  either  sex.  The  sex  of  almost  all  the  animals  used  is  indicated 
in  the  tables.  The  results  for  some  of  the  longer  series  are  sum- 
marized in  Table  7. 

It  is  very  doubtful  whether  there  is  any  direct  relationship 
between  the  body  weight  of  the  animal  and  the  concentration  of 
sugar  in  the  blood,  provided  that  the  animals  used  are  otherwise 
comparable.  It  must  be  borne  in  mind  that  variations  in  weight 
may  be  brought  about  by  an  abnormal  physical  condition,  e.g., 
tuberculosis,  and  conversely  these  variations  may  be  used  as  a 
means  of  detecting  such  abnormal  conditions.  A  study  of  Tables 
4  and  5  or  of  Table  8,  in  which  the  results  bearing  upon  this  point 
are  summarized,  reveals  the  fact  that  if  the  animals  are  divided 


292 


Ernest  Lyman  Scott 


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Content  of  Sugar  in  the  Blood  Under  Laboratory  Conditions    293 

into  two  series,  those  heavier  than  the  mean  and  those  hghter 
than  the  mean,  the  average  concentration  of  sugar  in  the  blood  of 
the  former  is  shghtly  higher  than  in  the  latter.  This  difference  is, 
however,  slight,  and  a  study  of  the  individual  variations  indicate 
that  there  is  no  direct  relationship  between  body  weight  and  the 
concentration  of  sugar  in  the  blood. 

TABLE  8 

Showing  the  Independence  of  Body  Weight  and  the  Concentration  of 

Sugar  in  the  Blood  of  Healthy  Cats 


Meat  fed  Gm.  %  of 
sugar 

Bread  and  meat 
Gm.  %  of  sugar 

Actual 

Calculated 
to  30  gm. 

Actual 

Calculated 
to  30  gm. 

Gm.   per  cent   for  heaviest   animal   in 
series    

.074 

.056 
2.93 
3.25 
2.00 

.076 

.066 

.071 

.064 
2.93 
3.25 
3.05 

.071 

.068 

.105 

r.ioo 

\.056 

2.77 
2.98 
2.50 

.085 

.072 

.102 

/.104 
\.056 

2.77 

2.50 

2.50 

.083 

.073 

Gm.    per   cent    for   lightest   animal   in 
series    

Average  body  wt.  for  series  k 

VVt.  of  animal  with  most  sugar 

Wt.  of  animal  with  least  sugar    

Gm.  per  cent  sugar  for  those  heavier 
than  mean  

Gm.   per  cent  sugar  for  those  lighter 
than  mean 

IV.  —  The  Content  of  Sugar  in  the  Blood  of  Standard 

Animals 

Before  an  interpretation  of  experimental  work  may  be  legiti- 
mately attempted,  a  standard  must  be  fixed  as  a  basis  for  compari- 
son. It  must,  however,  be  clearly  kept  in  mind  that  such  a 
standard  is  no  more  normal  than  many  other  values  which  might 
be  obtained.  One  ot  the  most  striking  characteristics  of  almost  all 
of  the  published  tables  showing  the  concentration  of  sugar  in  the 
blood  is  not  the  constancy  which  we  have  been  led  to  expect,  but 
a  variation  within  rather  wide  limits. 


294  Ernest  Lyman  Scott 

One  of  our  criteria  of  life  is  the  ability  of  the  organism  to  re- 
spond to  changes  in  the  environment.  That  is,  in  any  environ- 
ment, the  organism  tends  to  reach  a  condition  of  equilibrium  and  is 
successful  in  life  in  so  far  as  it  is  successful  in  maintaining  itself  in 
equilibrium  with  its  constantly  changing  environment.  This  has 
long  been  recognized  for  external  and  physical  conditions,  so  that 
one  would  hardly  say,  for  example,  that  an  animal  was  more 
normal  standing  than  walking,  or  asleep  than  awake.  But  internal, 
including  chemical,  readjustments  must  occur  which  are  just  as 
normal  as  are  the  more  obvious  physical  responses.  Mathews  has 
recently  spoken  of  the  general  bearing  of  this  class  of  adjustments. 
Cannon  ^  has  selected  the  concentration  of  sugar  in  the  blood  of 
animals  undergoing  emotional  disturbance  as  a  type  of  such  read- 
justment. He  holds,  and  with  reason,  that  there  may  be  as  much 
"purpose"  in  this  reflex  as  there  is  in  the  accompanying  muscu- 
lar response.  Indeed,  the  increased  amount  of  mobilized  sugar 
may  be  necessary  to  make  the  more  obvious  muscular  response 
possible. 

It  is  then  hopeless  to  think  of  finding  any  one  value  which  will 
be  closely  approximated  by  all  normal  animals.  However  this  may 
be,  the  more  nearly  we  subject  the  animals  to  a  standard  set  of 
conditions  before  the  sample  of  blood  is  obtained,  the  more  nearly 
we  may  expect  to  approach  a  constant  value.  With  organisms  so 
complex  as  are  the  mammals,  absolute  constancy  of  the  preliminary 
conditions  is  manifestly  impracticable,  and  so  we  can  hardly  expect 
an  absolutely  constant  value  for  the  concentration  of  sugar  in  the 
blood.  Again,  after  having  estabhshed  a  standard  value  for  the 
concentration  of  sugar  under  some  one  set  of  conditions,  modifica- 
tion of  any  one  or  more  of  the  factors  might  be  expected  to  give  a 
new,  but  none  the  less  normal,  value.  Thus  the  addition  of  bread 
to  the  diet  might  well  give  a  different  value  than  meat  alone 
(compare  Tables  4  and  5). 

The  method  of  preliminary  treatment  which  in  my  hands  has 
given  the  most  constant  results,  together  with  some  of  the  factors 
which  may  bring  about  variations,  has  already  been  described. 
The  results  are  given  in  Table  5  (compare  also  the  values  given  in 
Table  i).  Results  in  the  other  tables  are  to  be  compared  with 
those  in  Table  5  as  a  standard,  since  the  experiments  have  been 


Content  of  Sugar  in  the  Blood  Under  Laboratory  Conditions    295 

made  upon  animals  which  might  otherwise  have  been  presumed  to 
have  given  similar  results. 

These  considerations,  together  with  the  relation  between  the 
condition  of  the  sugar  in  the  blood  and  the  method  of  analysis, 
make  it  obvious  that  at  present  only  relative  values  for  the  con- 
centration of  sugar  in  the  blood  are  to  be  expected.  In  order  that 
the  results  of  a  research  may  be  comparable,  a  set  of  preliminary 
conditions,  which  have  been  shown  to  give  an  approximately  con- 
stant concentration  of  sugar,  must  be  selected  as  a  standard.  The 
exact  nature  of  these  conditions  will,  presumably,  be  determined, 
to  som^e  extent  at  least,  by  the  nature  of  the  particular  research  in 
hand.  Before  the  results  of  different  researches  may  be  properly 
compared,  they  must  be  reduced  to  similar  terms.  This  may  be 
done  by  a  factor  of  comparison  similar  to  the  one  described  on 
page  277,  but  which  includes  the  preliminary  conditions  as  well  as 
the  method  of  analysis. 

There  seem  to  have  been  but  comparatively  few  determinations 
of  the  sugar  in  cat's  blood.  Boehm  and  Hoffmann  made  26  ob- 
servations on  blood  drawn  from  the  carotid  without  anesthesia. 
Their  results  are,  as  one  would  expect,  high,  varying  between  o.ii 
per  cent  and  0.31  per  cent.  They  may  well  be  considered  ex- 
amples of  emotional  hyperglycaemia  and  should  be  compared  with 
my  results  given  in  Table  3,  rather  than  with  the  standard  results 
in  Table  5.  Rona  and  Takahashi  report  analyses  of  the  blood  from 
four  cats.  They  too  drew  the  blood  from  the  carotid,  but  under 
light  narcosis.  The  concentrations  which  they  found  are  quite 
comparable  in  magnitude  with  those  of  Boehm  and  Hoffmann, 
varying  between  0.154  per  cent  and  0.355  P^^  cent.  The  high 
concentration  here  is,  however,  probably  due  to  the  anesthetic  and 
should  be  compared  with  results  shown  in  Tables  10-12  rather  than 
with  my  standard  results.  Pavy  ^  gives  the  results  of  six  analyses 
of  blood  taken  from  the  heart  after  pithing.  The  values  vary 
between  0.068  per  cent  and  0.1026  per  cent,  with  a  mean  of  0.088 
per  cent.  Since  the  type  of  diet  and  general  preliminary  treat- 
ment are  not  given,  one  cannot  tell  to  what  extent  his  results  are 
comparable  with  mine,  or  whether  they  should  be  compared  with  my 
standard  or  with  the  results  for  cats  fed  on  bread  and  meat  which 
are  given  in  Table  4.    The  above  results  are  summarized  in  Table  9. 


296 


Ernest  Lyman  Scott 


TABLE  9 

Table  Giving  Summary  of  Concentrations  of  Sugar  in  Cat's  Blood  Found 

BY  Different  Observers 


Observer 

Manner  of 
collection 

No.  of 
observa- 
tions 

Mean 
concen- 
tration 
in% 

Highest 
concen- 
tration 

Lowest 
concen- 
tration 

Observations 

which  vary  from 

average  by  more 

than  10% 

Abso- 
lute no. 

%of 

whole 

no. 

Boehm  and 
Hoffmann  . 

R  0  n  a     and 
Takahashi  . 

Pavy 

Scott 

From   carotid    no 
anesthesia     .... 

From  carotid  light 
narcosis    

From  heart   after 
pithing 

From  neck  vessels 
after  decapitation 

26 

4 
6 

22 

0.15 

0.282 
0.088 
0.069 

0.31 
0.355 
0.103 
0.096 

0.11 
0.154 
0.068 
0.056 

21(?) 
3 
5 
4 

81 
75 
83 
18 

V.  —  The  Relation  of  a  Few  of  the  Ordinary  Experimental 
Procedures  to  the  Concentration  of  Sugar  in  the 
Blood 

From  what  has  been  said  it  will  be  seen  that  any  experiment 
which  involves  the  estimation  of  the  sugar  in  the  blood  would  be 
valueless  if  the  animal  is  subjected  to  pain  or  other  form  of  excite- 
ment during  the  course  of  the  experiment  or  within  a  few  hours 
previous  to  it.  It  will  also  be  noted  that  this  is  quite  apart  from 
any  humanitarian  considerations.  Any  work  therefore  which  would 
otherwise  involve  pain  must  be  accompanied  by  an  anesthetic. 
This  at  once  brings  up  the  question  of  the  effect  of  the  anesthetic 
itself. 

That  ether,  occasionally  at  least,  causes  glycosuria  in  patients 
undergoing  operations  has  been  known  almost  from  the  beginning 
of  its  use  as  an  anesthetic.  Harley  and  Tiegel  very  early  demon- 
strated glycosuria  in  animals  to  which  ether  had  been  given. 
Hawk  maintains  that  it  always  occurs  in  dogs  when  ether  is  used 
as  an  anesthetic,  and  his  statements  have  been  confirmed  by  Seehg. 


Content  of  Sugar  in  the  Blood  Under  Laboratory  Cofiditions     297 

Underbill  publishes  figures  showing  an  increase  in  the  concentration 
of  sugar  in  the  blood  of  two  dogs  which  had  received  ether. 

The  fact  that  the  administration  of  ether  is  accompanied  by 
hyperglycaemia  does  not  of  itself  preclude  its  use  in  experiments 
of  this  character.  If  a  set  of  conditions  —  of  which  ether  is  one  — 
can  be  found  that  meets  the  requirements  of  a  standard,  it  would 
seem  that  the  use  of  ether  would  be  legitimate.  In  the  use  of 
ether,  difficulty  is  at  once  encountered  in  getting  the  animal  under 
the  influence  of  the  drug  without  introducing  other  disturbing 
factors.  In  Table  3  it  was  shown  that  the  rigid  holding  of  the 
animal  necessary  in  the  use  of  the  cone  for  this  purpose  is  produc- 
tive of  a  significant  disturbance  in  the  concentration  of  sugar  in 
the  blood.  Likewise,  in  the  single  case  tried,  a  similar  result  was 
obtained  when  the  animal  was  confined  under  a  bell  jar.  This 
particular  animal,  however,  resented  the  confinement.  It  was 
found  that  by  careful  selection  of  individuals  those  could  be  found 
which  so  far  as  one  could  tell  were  not  disturbed  by  the  brief 
restraint  necessary.  The  bell  jar  has  the  disadvantage  of  offering 
greater  danger  of  partial  asphyxiation  than  does  the  cone,  and  it 
has  been  abundantly  shown  that  asphyxia  of  itself  is  sufficient  to 
cause  hyperglycaemia  (cf.  Bang).  It  was  thought  that  with  proper 
precautions  any  danger  of  asphyxia  could  be  avoided  and  that 
aside  from  this  there  were  fewer  objections  to  the  use  of  the  bell 
jar.  Consequently  in  all  of  my  experiments,  where  ether  or 
chloroform  was  given,  the  animal  was  put  in  a  bell  jar  for  the 
initial  stages.  The  animals  were  removed  from  the  jar  as  soon  as 
muscular  relaxation  had  occurred.  When  the  anesthetic  was  to  be 
given  for  a  longer  time,  this  was  done  by  means  of  a  cone.  As- 
phyxia was  avoided  either  by  very  rapid  anesthetization  in  a  jar  of 
fairly  large  volume  or  by  the  admission  of  air  below  the  jar  when 
slower  anesthetization  was  desired. 

The  results  for  animals  prepared  in  the  standard  manner  are 
shown  in  Table  10.  It  is  evident  that  there  is  no  approximation  to 
a  constant.  And  in  addition  to  this  the  animals  to  which  ether  was 
given  for  30  minutes  have  a  distinctly  higher  concentration  of  sugar 
in  their  blood  than  those  to  which  it  was  administered  for  only  three 
minutes  or  less.  This  indicates  a  cumulative  effect  of  .the  ether, 
which  would  still  further  confuse  the  results  of  the  experiment. 


298 


Ernest  Lyman  Scott 


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Content  of  Sugar  in  the  Blood  Under  Laboratory  Conditions    299 

Seelig  reports  that  ether  gives  much  less  trouble  in  this  way 
with  dogs  which  have  been  fed  on  bread  for  some  time  than  with 
those  which  have  been  on  a  meat  diet.  Macleod  also  has  sought 
to  avoid  the  disturbing  effect  of  ether  in  the  same  way.  The 
results  which  I  have  obtained  with  cats  fed  on  the  bread  and 
meat  diet  described  on  page  281  are  shown  in  Table  11.  A  compari- 
son of  these  results  with  those  given  in  the  preceding  table  shows 
that  while  there  is  still  so  much  variation  that  they  would  be  un- 
satisfactory as  a  basis  for  experimental  results,  they  are  more 
uniform  than  those  obtained  with  the  meat  diet.  Also  the  cumula- 
tive ejffect  of  the  ether  is  not  so  great. 

A  definite  relation  between  the  ease  with  which  the  equiHbrium 
of  the  mobile  carbohydrates  of  the  body  is  disturbed  and  the  type 
of  diet  given  the  animal  would  be  of  considerable  theoretical  in- 
terest. Such  a  difference  must  imply  a  difference  either  in  the 
chemical  form  of  the  carbohydrate  or  in  the  tissues  in  which  it  is 
stored.  This  theoretical  interest,  together  with  the  opportunity 
which  might  be  offered  the  experimentaUst  of  reducing  the  varia- 
tions to  a  minimum,  would  warrant  sufficient  work  to  establish 
either  the  existence  or  non-existence  of  such  a  relation.  This  is 
especially  true,  since  Seehg's  results  agree  with  those  given  above 
in  indicating  the  hopeful  outcome  of  such  a  research. 

The  results  given  in  Table  12  were  obtained  from  animals  which 
were  to  be  used  by  a  class  of  medical  students.  These  animals 
were  killed  by  decapitation  as  usual,  but  without  special  prepara- 
tion. The  first  eight  were  anesthetized  by  ether  in  a  bell  jar  in 
the  usual  manner  by  the  students.  As  soon  as  muscular  relaxation 
had  occurred,  they  were  removed  from  the  jar  and  decapitated  at 
once.  The  last  five  were  used  for  demonstration  purposes  and  had 
been  under  ether  for  periods  varying  from  an  hour  to  three  or  four 
hours,  during  which  time  the  operation  indicated  had  been  done. 
Since  these  animals  were  primarily  used  for  other  purposes,  I  was 
unable  to  record  the  full  data.  The  results  are,  however,  given  in 
the  hope  that  they  will  prove  of  some  value,  indicative  as  they  are 
of  the  results  which  may  be  expected  under  ordinary  laboratory 
conditions.  Chloroform  does  not  seem  to  offer  any  advantages 
over  ether  (Harley)  and  has  the  disadvantage  of  a  greater  toxicity. 
A  few  experiments  of  my  own,  hkewise,  give  no  indication  of  any 


300 


Ernest  Lyman  Scott 


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Content  of  Sugar  in  the  Blood  Under  Laboratory  Conditions    301 


TABLE  12 

Effect  of  Ether  on  Concentration  of  Sugar  in  Blood  of  Cats  which  Have 
Received  no  Especial  Preparation 


No.  of 
Exp. 

Sex 

Body 
wt.  k. 

Amt.  of 

blood 

gm. 

Concen- 
tration 
sugar 
gm.  % 

Per  cent  of  variation 
from  mean  of 

Remarks 

This 
series 

Stand, 
series 

Bread 
and 
meat 

series 

37 

M 

— 

80.05 

0.106 

-    8 

+    54 

+    38 

38 

F 

— 

75.25 

0.104 

-10 

+    51 

+    33 

39 

M 

— 

97.25 

0.151 

+  31 

+  119 

+    94 

40 

F 

— 

52.60 

0.094 

-18 

+    36 

+    21 

41 

M 

— 

,  80.60 

0.123 

+    7 

+    78 

+    58 

42 

M 

— 

63.25 

0.133 

+  16 

+    93 

+    71 

43 

F 

49.45 

0.126 

+  10 

+    83 

+    62 

44 

F 

62.05 

0.084 

-27 

+    22 

+     8 

Mean 

— 

— 

— 

0.115 

— 

+    67 

+    47 

251 

— 

— 

91.25 

0.129 

-40 

+    87 

+    65 

Pleural  puncture, 
treacheotomy 

571 

M 

3.00 

80.89 

0.134 

-38 

+    94 

+    72 

Decortication 

621 
841 

M 
M 

3.25 
2.80 

55.66 
79.92 

0.239 
0.298 

+  11 
+  39 

+  246 

+  332 

+  206 

+  282 

Decortication  less  ether 
than  no.  57 

851 
Mean 

M 

2.75 

72.80 

0.274 
0.215 

+  27 

+  300 

+  212 

+  251 
+  176 

Respiration  stopped 
under  ether 

1  These  animals  were  used  for  class  demonstration  and  were  under  ether  for  at  least 
one  hour  and  in  addition  were  subjected  to  the  operations  indicated. 

advantage  to  be  derived  from  its  use,  since  the  results  are  essen- 
tially similar  to  those  obtained  by  the  use  of  ether  (Table  13). 

Because  of  its  stimulating  action  on  the  cat,  no  one  would 
think  of  making  use  of  morphine  in  drawing  blood  from  this 
particular  animal.  It  is,  however,  of  interest  to  note  that  Luzzatto 
finds  glycosuria  following  the  use  of  morphine  in  rabbits.  This 
finding  is  confirmed  by  Araki,  who  also  reports  similar  results  for 


302 


Ernest  Lyman  Scott 


TABLE  13 


The  Relation  between  Chloroform  and  the  Concentration  of  Sugar  in 
THE  Blood  of  Animals  Prepared  in  the  Standard  Manner 


No. 

of 

Exp. 

Sex 

Body 
wt.k. 

Time  in  min. 
from  applica- 
tion of  chloro- 
form to 

Amt.  of 

blood 

drawn 

gm. 

Concen- 
tration 
sugar 
gm.  % 

%  var.  from 
mean 

Remarks 

Muse,  re- 
laxation 

Death 

This 
series 

Stand, 
series 

87 

88 

97 

Mean 

M 

M 
F 

3.79 
3.50 
2.75 

5.0 
2.0 
1.5 

5.17 
2.67 
1.57 

78.05 
67.94 
62.96 

0.105 
0.098 
0.142 
0.115 

-    9 

-15 
+  23 

+    52 
+    42 
+  105 
+   67 

Unusually  quiet 
before  and  during 
anesthetization 

dogs,  though  he  found  no  sugar  in  the  urine  of  frogs  after  morphine. 
On  the  other  hand,  Hirsch  and  Reinbach  think  that  morphine  is 
without  effect  on  the  concentration  of  sugar  in  the  blood  of  rabbits. 
Jacobsen  found  an  undoubted  increase  in  the  amount  of  sugar  in 
the  blood  of  rabbits  to  which  sufficient  chloral  had  been  given  to 
produce  narcosis. 

Some  investigators  have  collected  blood  from  one  of  the  large 
vessels  under  the  local  anesthesia  produced  by  cocaine  (Fisher  and 
Wishart).  For  some  types  of  experiment,  such  a  method  is 
particularly  desirable,  provided  the  equiHbrium  of  the  mobile  sugar 
is  not  disturbed  by  the  drug  in  such  a  manner  that  the  proper 
allowances  cannot  be  made.  Araki  found  lactic  acid  in  the  urine 
of  frogs  and  of  rabbits  after  the  injection  of  cocaine.  One  of  the 
four  rabbits  injected  also  secreted  sugar  with  the  urine.  In  the 
present  work  four  cats  were  injected  beneath  the  skin  of  the  back 
with  large  doses  of  cocain  hydrochloride  dissolved  in  N/8  sodium 
chloride  solution.  These  animals  were  all  killed  in  the  early  stages 
of  the  apparent  reaction  to  the  drug.  (See  Table  14  for  details.) 
With  one  exception  each  of  the  concentrations  of  sugar  found  was 
well  below  the  standard  concentration.  The  mean  concentration 
for  the  series  is  86  per  cent  of  the  standard  mean.  Any  attempt 
to  explain  this  finding  woulP  be  premature,  since  a  longer  series 


Content  of  Sugar  in  the  Blood  Under  Laboratory  Conditions    303 


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0 

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304  Ernest  Lyman  Scott 

might  yield  results  which  would  essentially  modify  the  situation. 
Also  too  little  is  known  at  present  of  the  other  factors  of  metab- 
olism during  intoxication  by  cocaine  to  warrant  such  an  attempt. 

In  following  the  progress  of  an  experiment  it  is  frequently 
desirable  to  determine  the  changes  in  the  concentration  of  the 
sugar  in  the  blood  at  frequent  intervals.  Unfortunately  there  is, 
however,  a  very  serious  objection  to  this  procedure.  Claude 
Bernard  found  that  the  concentration  of  sugar  is  increased  by  a 
previous  hemorrhage,  and  his  finding  has  been  repeatedly  con- 
firmed. Recently  fairly  exhaustive  studies  have  been  made  by 
several  authors.  Among  others  Anderson,  Jacobsen,  Rose  and 
Schenck  have  studied  this  effect  in  rabbits.  Anderson  found  an 
increased  concentration  of  sugar  five  minutes  after  the  hemorrhage, 
but  did  not  determine  whether  it  was  present  after  a  still  shorter 
interval.  The  consensus  of  opinion  is  that  the  concentration 
reaches  its  maximum  about  thirty  minutes  after  the  hemorrhage 
and  that  it  remains  high  from  three  to  four  hours. 

Undoubtedly  emotional  disturbances  have  frequently  contrib- 
uted a  large  share  to  the  so-called  hemorrhage  hyperglycaemia. 
However  this  may  be,  there  is  no  doubt  that  quite  apart  from  any 
disturbance  due  to  emotion  or  to  anesthetics,  hemorrhage  does 
introduce  a  modification  for  which  proper  controls  must  be  made. 
Some  authors  have  sought  to  avoid  the  introduction  of  the  factor 
of  hemorrhage  by  the  use  of  a  quantity  of  blood  so  small  that  it 
might  be  considered  as  negligible,  but  this  so  greatly  increases  the 
probable  error  from  analytical  technique  that  the  method  has  a 
questionable  value,  at  least  for  most  methods  of  analysis.  Further- 
more the  objection  to  repeated  handling  of  the  animal  and  the 
consequent  excitement  are  not  met  by  the  change  in  analytical 
method,  and  demand  exceptional  skill  on  the  part  of  the  experi- 
menter. The  literature  covering  this  subject  is  so  ample  and,  taken 
as  a  whole,  so  conclusive  that  it  was  not  thought  necessary  to  add 
to  it. 

Changes  in  the  concentration  of  the  sugar  in  the  blood  may  be 
used  as  a  measure  of  the  effect  of  a  substance  which  has  been  in- 
jected into  the  animal.  In  such  experiments  it  is  usually  presumed 
that  the  effect  of  the  injection  aside  from  the  drug  is  nil.  My  own 
experiments  are  too  few  in  number  to  allow  of  general  conclusions. 


Content  of  Sugar  in  the  Blood  Under  Laboratory  Conditions    305 

But  in  harmony  with  the  rest  of  my  work  they  indicate  the  neces- 
sity of  complete  control  of  all  factors  in  the  experiment.  Long 
ago  Bock  and  Hoffmann  showed  that  large  amounts  of  salt  solution 
caused  glycosuria  when  injected  intravenously.  But  while  drugs 
are  frequently  dissolved  in  a  solution  of  sodium  chloride  for  injec- 
tion, the  effect  of  the  salt  solution  is  essentially  different  from  that 
obtained  by  Bock  and  Hoffmann,  since  usually  very  much  smaller 
amounts  are  injected.  In  my  own  experiments  with  cocaine  cer- 
tainly no  factor  was  introduced  which  increased  the  concentration 
of  sugar  enough  to  conceal  the  results  due  to  the  cocaine  alone,  with 
the  possible  exception  of  one  animal.  (See  Table  14.)  Especial 
care  was  taken  in  making  these  injections  of  cocaine  to  avoid  excit- 
ing the  animal.  The  same  care  was  exercised  in  an  animal  which 
was  injected  with  5  cc.  of  M/8  sodium  chloride.  This  cat  was 
killed  five  hours  later,  and  the  blood  yielded  a  concentration  of 
sugar  of  0.0697  per  cent,  a  result  almost  exactly  the  same  as  the 
standard.  Another  animal  injected  through  an  opening  in  a  small 
box  in  which  it  was  confined  with  the  same  amount  of  sodium 
chloride  solution  became  much  excited.  This  animal,  after  the 
lapse  of  a  similar  interval,  yielded  a  concentration  of  0.098  per 
cent  —  a  much  higher  result  than  the  standard. 

Again,  many  experiments  of  this  nature  involve  the  confinement 
of  the  animal  within  some  form  of  apparatus.  The  exact  results 
obtained  in  animal  calorimetry  are  ample  evidence  of  the  availability 
of  this  type  of  research.  On  the  other  hand,  great  care  is  necessary 
to  avoid  exciting  the  animal.  This  is  illustrated  in  the  two  animals 
exposed  to  cold  as  described  on  page  291.  While  they  were  exposed 
to  similar  external  conditions,  one  became  very  restless  and  yielded 
a  concentration  of  0.149  P^^  cent  of  sugar;  the  other  remained 
exceptionally  quiet  and  yielded  a  concentration  of  only  0.049  per 
cent.  The  nature  of  this  experiment,  together  with  the  results, 
would  suggest  the  possibihty  that  the  unpleasant  conditions  in- 
volved constitute  at  least  one  of  the  factors  leading  to  the  mobiliza- 
tion of  the  sugar  in  Lusk's  method  of  ridding  the  body  of  glycogen 
by  shivering. 

In  another  experiment  four  cats  were  ccnfined  in  a  respiratory 
chamber  and  subjected  to  a  temperature  of  about  32°  C.  and  a 
relative  humidity  of  about  88  per  cent.     The  results  are  shown  in 


3o6 


Ernest  Lyman  Scott 


Table  15.  Animals  were  selected  for  these  experiments  which  might 
be  expected  to  remain  quiet  throughout  the  experiment.  No.  112 
was  the  only  one  which  proved  disappointing  in  this  regard.  The 
results  show  an  exceptionally  low  average  for  the  concentration  of 
sugar,  and  this  individual  is  the  only  one  of  the  four  which  reached 
the  level  of  the  standard  cats. 

TABLE    15 

The  Effect  of  the  Confinement  of  Cats  in  a  Warm,  Moist  Chamber 
UPON  THE  Concentration  of  Sugar  in  the  Blood 


No. 

of 

Exp. 

Sex 

Body 
wt.  k. 

Amt.  of 

blood 

drawn 

gm. 

Hrs.  in 
chamber 

Temp. 

mean 

C. 

Rel.  hu- 
midity 
mean 

Concen- 
tration 
sugar  in 
blood 
gm.  % 

%of 
var. 
from 
stand, 
mean 

Cal.  for  30  gm. 

blood  per  k. 

body  wt. 

Concen- 
tration 
sugar 

%  var. 
from 
stand. 

gm.  % 

average 

Ill 

F 

3.65 

83.38 

6 

30.6 

.83 

0.053 

-23 

0.049 

-29 

1121 

F 

1.62 

55.57 

6 

30.7 

.89 

0.064 

-    7 

0.067 

-3 

113 

F 

3.78 

69.87 

6 

33.1 

.90 

0.065 

-    6 

0.058 

-16 

114 

F 

2.90 

65.12 

6 

32.9 

.90 

0.059 

-  14 

0.054 

-22 

Mean 

— 

— 

— 

31.8 

.88 

0.060 

-  13 

0.057 

-  16 

1  Excited  when  removed  from  the  chamber. 

There  seems  then  to  be  no  reason  for  attributing  changes  in  the 
concentration  of  the  sugar  in  the  blood  following  the  injection  of 
small  amounts  of  salt,  or  the  confinement  of  the  animal  in  appa- 
ratus to  these  conditions  of  themselves.  Excitement  induced  by 
these  conditions  may,  however,  give  rise  to  high  concentrations, 
even  five  hours  after  the  time  of  irritation. 


VI.  —  Summary  and  Conclusions 

I.  Glycaemia  offers  a  more  satisfactory  indication  of  the  condi- 
tion of  mobile  sugar  than  does  glycosuria;  first,  because  either 
an  increase  or  a  decrease  in  the  amount  of  sugar  may  be  demon- 
strated, while  normal  urine  can  show  only  an  increase;    secondly, 


Content  of  Sugar  in  the  Blood  Under  Laboratory  Conditions    307 

because  profound  changes  in  glycaemia  may  occur  in  response  to 
conditions  which  do  not  produce  glycosuria;  thirdly,  the  blood  is 
in  much  more  direct  relation  to  the  living  cells  than  is  the  urine. 

2.  The  concentration  of  sugar  in  the  blood  as  estimated  by  dif- 
ferent methods  varies.  This  may  be  due,  in  part  at  least,  to  the 
form  in  which  the  sugar  is  present  in  the  blood.  It  follows  that 
results  obtained  by  different  methods  of  analysis  cannot  properly 
be  com.pared  until  they  have  been  reduced  to  common  terms. 
Also  the  possibility  is  introduced  of  an  apparent  variation  in  con- 
centration of  sugar,  even  when  the  method  of  estimation  is  constant, 
which  is  due  to  a  change  in  the  form  in  which  the  sugar  is  present 
rather  than  to  a  change  in  the  actual  amount  of  sugar  present. 

3.  If  consistent  results  are  to  be  expected,  the  animals  must  be 
uniformly  healthy,  and  must  be  killed  without  pain  or  excitement. 
Sex  or  weight,  apart  from  correlated  conditions,  are  probably  with- 
out special  influence  upon  the  concentration  of  sugar  in  the  blood. 

4.  The  normal  concentration  of  sugar  may  very  probably  vary 
with  the  varying  environment  of  the  animal  or  with  changes  in  its 
physical  state.  However,  if  the  environment  is  uniform  and  if  the 
animals  are  killed  while  in  the  same  physiological  condition,  con- 
stant results  should  be  expected.  Practically  such  an  ideal  result 
is  not  possible,  but  has  been  approached  with  some  success. 

5.  The  concentration  of  sugar  in  the  blood  decreases  as  the 
amount  of  blood  drawn  per  kilo  of  body  weight  of  the  animal 
increases.  So  far  sufficient  data  have  not  been  obtained  to  es- 
tablish the  mathematical  expression  for  this  relation. 

6.  When  ether  or  chloroform  was  administered,  the  concentra- 
tion of  sugar  was  increased  considerably  and  varied  between 
rather  wide  limits,  whether  the  diet  consisted  of  meat  alone,  or  of 
bread  and  meat,  the  latter  diet  giving  somewhat  smaller  variations 
than  the  former.  After  either  diet  there  was  a  greater  concentra- 
tion after  the  drug  had  been  administered  for  thirty  minutes  than 
after  it  had  been  administered  for  three  minutes  or  less. 

7.  The  concentration  of  sugar  in  the  blood  after  subcutaneous 
injection  of  cocaine  is  more  constant  than  that  found  after  inhala- 
tion of  ether  or  chloroform  and  is  lower  than  that  found  in  animals 
similarly  treated  but  to  which  cocaine  has  not  been  given. 

8.  It  may  be  shown  from  the  literature  that  hyperglycaemia 


3o8  Ernest  Lyman  Scott 

follows  hemorrhage.  From  this  it  follows  that  caution  must  be 
exercised  in  drawing  conclusions  from  experiments  which  involve 
the  analysis  of  successive  samples  of  blood. 

9.  The  excitement  which  is  apt  to  attend  hypodermic  injections 
or  confinement  in  apparatus  may  lead  to  high  results  and  conse- 
quently to  false  conclusions,  With  care,  however,  such  effects  may 
be  avoided  so  that  this  type  of  experiment  is  permissible. 

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3IO  Ernest  Lyman  Scott 

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Archiv  fiir  die  gesammte  Physiologie,  1894,  Ivii,  553-572. 

Seelig,  a.:  Ueber  Aetherglykosurie  und  ihre  Beeinflussung  durch  intra- 
venose  Sauerstoffinfusionen,  Archiv  fiir  Experimentelle  Pathologie  und  Phar- 
makologie, 1905,  lii,  481-494. 

Stewart,  G.  N.,  C.  C.  Guthrie,  R.  L.  Burns,  and  F.  H.  Pike:  The 
resuscitation  of  the  central  nervous  system  of  mammals.  Journal  of  Experi- 
mental Medicine,  1906,  viii,  289-321. 

Stewart,  G.  N.,  and  F.  H.  Pike:  Resuscitation  of  the  respiratory  and 
other  bulbar  nervous  mechanisms,  with  special  reference  to  the  question  of 
their  automaticity,  American  Journal  of  Physiology,  1907,  xix,  328-359. 

TiEGEL,  E.:  Ueber  eine  Fermentwirkung  des  Blutes,  Archiv  fiir  die  ge- 
sammte Physiologie,  1872,  vi,  249-266. 

Underhill,  F.  p.:  Certain  aspects  of  experimental  diabetes,  Journal  of 
Biological  Chemistry,  1905,  i,  11 5-130. 


VITA 

I  WAS  born  on  August  i8th,  1877,  in  Kinsman,  Ohio,  and  graduated 
from  the  Kinsman  High  School  with  the  class  of  1897.  In  1902 
I  received  the  degree  of  Bachelor  of  Science  from  Ohio  Wesleyan 
University.  Immediately  upon  graduation  I  entered  the  United 
States  Coast  and  Geodetic  Survey.  While  in  this  service  the  greater 
part  of  my  time  was  spent  in  hydrographic  work  in  Chesapeake 
Bay. 

I  began  my  duties  as  instructor  in  sciences  in  the  Western  High 
School,  Bay  City,  Michigan,  in  September,  1903,  and  remained  there 
until  April,  1910,  when  I  accepted  a  fellowship  in  the  Department  of 
Physiology  of  the  University  of  Chicago.  With  the  beginning  of  the 
following  summer  quarter  my  rank  was  raised  to  that  of  assistant. 
While  in  the  University  of  Chicago  a  part  of  my  time  was  taken  up 
with  instruction  in  laboratory  courses  and  a  part  was  given  to  study 
and  research.  In  the  spring  of  191 1  I  was  elected  to  Sigma  Xi  and 
at  the  close  of  the  summer  quarter  received  the  degree  of  Master  of 
Science.  My  thesis,  which  represented  an  experimental  investigation 
of  the  influence  of  intravenous  injections  of  an  extract  of  the  pancreas 
on  experimental  pancreatic  diabetes,  was  pubUshed  in  the  American 
Journal  of  Physiology,  volume  twenty-nine,  191 2. 

In  the  autumn  of  191 1  I  entered  upon  my  duties  as  assistant 
professor  of  physiology  in  the  University  of  Kansas.  At  the  close  of 
one  year  I  resigned  this  position  to  accept  an  instructorship  in  physi- 
ology in  Columbia  University.  I  have  now  been  advanced  to  an 
associateship  in  Columbia  for  19 14-15. 

(Signed)     ERNEST   LYMAN   SCOTT 

May  10,  1914. 


COLUMBIA  UNIVERSITY  LIBRARIES 

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